Combination Therapy Of Inhaled Corticosteroids Research Articles

Genetic evaluation of the effect of GLCCI1 rs37973 on corticosteroid response in chronic obstructive pulmonary disease

BackgroundThe efficacy of inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD) varies between patients, which may be partially due to genetic differences. A single-nucleotide polymorphism, rs37972, in the glucocorticoid-induced transcript 1 gene (GLCCI1) has been associated with variations in response (forced expiratory volume in 1 s [FEV1] and residual volume) to fluticasone propionate (Groningen and Leiden Universities Study of Corticosteroids in Obstructive Lung Disease [GLUCOLD] study). The aim of this study was to determine whether variation in the GLCCI1 gene at rs37973 is associated with ICS response in patients with COPD.MethodsVariations in the GLCCI1 gene, rs37973 (which is in almost complete linkage disequilibrium with rs37972) were examined in 402 corticosteroid-treated, non-Hispanic Caucasian COPD patients, and in 63 GLUCOLD study patients.ResultsWe were unable to confirm a genetic association between GLCCI1 and change in FEV1, unlike equivalent data generated for rs37973 from the GLUCOLD study sample. This was despite accounting for differences in gender, baseline FEV1, severity of COPD, extent of reversibility, and combination therapy of ICS with bronchodilators.ConclusionsWe conclude that based on changes in FEV1, there is no evidence that the GLCCI1 variant rs37973 has an impact on corticosteroid response in patients with COPD.Trial registrationGSK study number HZC112206 (ClinicalTrials.gov identifier: NCT01053988. Registered January 14 2010) and HZC112207 (ClinicalTrials.gov identifier: NCT01054885. Registered January 14 2010).

Prevention of acute exacerbations of chronic obstructive pulmonary disease

Objective Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are significant events which are associated with worsened quality of life and more rapid decline in lung function. And they also can increase mortality and health care costs. Pharmacologic interventions can alter the frequency of AECOPDs and COPD-related hospitalizations, mainly by focusing on three ways: antiinfective agents, antiinflammatory agents and antioxidants which also become the chief clue to the current researches for new drugs and therapies. The combination therapy of inhaled corticosteroids and long-acting β2-adrenoceptor agonists is the most widely recommended strategy for acute exacerbation prevention. But the inhaled corticosteroids possibly increase the risk for pneumonia. Further studies are needed to understand the mechanism of benefit in patient subpopulations, and to compare between efficacy of combination therapy and side-effect with inhaled corticosteroids, bronchodilators, or their combination in different patient phenotypes. We must have a better understanding of the heterogeneity implicit for COPD and the types of COPD exacerbations, and individualized treatments need to be investigated. Key words: Pulmonary disease chronic obstructive; Universal prevention

Combination long-acting β-agonists and inhaled corticosteroids compared with long-acting β-agonists alone in older adults with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a manageable respiratory condition, is the third leading cause of death worldwide. Knowing which prescription medications are the most effective in improving health outcomes for people with COPD is essential to maximizing health outcomes. To estimate the long-term benefits of combination long-acting β-agonists (LABAs) and inhaled corticosteroids compared with LABAs alone in a real-world setting. Population-based, longitudinal cohort study conducted in Ontario, Canada, from 2003 to 2011. All individuals aged 66 years or older who met a validated case definition of COPD on the basis of health administrative data were included. After propensity score matching, there were 8712 new users of LABA-inhaled corticosteroid combination therapy and 3160 new users of LABAs alone who were followed up for median times of 2.7 years and 2.5 years, respectively. Newly prescribed combination LABAs and inhaled corticosteroids or LABAs alone. Composite outcome of death and COPD hospitalization. The main outcome was observed among 5594 new users of LABAs and inhaled corticosteroids (3174 deaths [36.4%]; 2420 COPD hospitalizations [27.8%]) and 2129 new users of LABAs alone (1179 deaths [37.3%]; 950 COPD hospitalizations [30.1%]). New use of LABAs and inhaled corticosteroids was associated with a modestly reduced risk of death or COPD hospitalization compared with new use of LABAs alone (difference in composite outcome at 5 years, -3.7%; 95% CI, -5.7% to -1.7%; hazard ratio [HR], 0.92; 95% CI, 0.88-0.96). The greatest difference was among COPD patients with a codiagnosis of asthma (difference in composite at 5 years, -6.5%; 95% CI, -10.3% to -2.7%; HR, 0.84; 95% CI, 0.77-0.91) and those who were not receiving inhaled long-acting anticholinergic medication (difference in composite at 5 years, -8.4%; 95% CI, -11.9% to -4.9%; HR, 0.79; 95% CI, 0.73-0.86). Among older adults with COPD, particularly those with asthma and those not receiving a long-acting anticholinergic medication, newly prescribed LABA and inhaled corticosteroid combination therapy, compared with newly prescribed LABAs alone, was associated with a significantly lower risk of the composite outcome of death or COPD hospitalization.

Phosphodiesterase 4 Inhibitors Augment the Ability of Formoterol to Enhance Glucocorticoid-Dependent Gene Transcription in Human Airway Epithelial Cells: A Novel Mechanism for the Clinical Efficacy of Roflumilast in Severe Chronic Obstructive Pulmonary Disease

Post-hoc analysis of two phase III clinical studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequency in patients with severe chronic obstructive pulmonary disease (COPD) who were taking inhaled corticosteroids (ICS) concomitantly, whereas patients not taking ICS derived no such benefit. In contrast, in two different trials also performed in patients with severe COPD, roflumilast reduced exacerbation rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic activity to be realized. Given that roflumilast is recommended as an "add-on" medication to patients with severe disease who will inevitably be taking a long-acting β2-adrenoceptor agonist (LABA)/ICS combination therapy, we tested the hypothesis that roflumilast augments the ability of glucocorticoids to induce genes with anti-inflammatory activity. Using a glucocorticoid response element (GRE) luciferase reporter transfected into human airway epithelial cells [both bronchial epithelium + adenovirus 12 - SV40 hybrid (BEAS-2B) cells and primary cultures], roflumilast enhanced fluticasone propionate-induced GRE-dependent transcription. Roflumilast also produced a sinistral displacement of the concentration-response curves that described the augmentation of GRE-dependent transcription by the LABA formoterol. In BEAS-2B cells and primary airway epithelia, roflumilast interacted with formoterol in a positive cooperative manner to enhance the expression of several glucocorticoid-inducible genes that have anti-inflammatory potential. We suggest that the ability of roflumilast and formoterol to interact in this way supports the concept that these drugs together may impart clinical benefit beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy. Roflumilast may, therefore, be especially effective in patients with severe COPD.

A Successful Case of Persistent Asthma in the Treatment of Inhalation Corticosteroid Combination Therapy of Budesonide/Folmoterol and Ciclesonide

A-60 years old woman has been observed in our outpatient clinic for several years. She has been uncontrolled for her asthma despite multi-drug therapy; [Fluticazone (FP) 800 μg/day+Salmeterol(SM l00 μg+Montelukast 10 mg+Theophilline 200 mg/day], presenting asthma control test (ACT) score as 13. We added Ciclesonide (CIC) to her therapy and replaced FP and SM with BFC. As a result, her pulmonary function and ACT score improved. The counts of eosinophils in induced sputum decreased significantly. Furthermore, during an observation period of 9 months, she had neither had an emergency visit nor an asthma exacerbation. While some physicians previously reported efficacy of Inhaled corticosteroids (ICS) combination therapy of FP and Beclomethasone (BDP), there are no reports concerning the efficacy and tolerability of ICS combination therapy of Budesonide/Folmoterol combination (BFC) and Ciclesonide-hydrofluoroalkane (CIC-HFA). This is the first case report of a persistent asthma patient succesfully treated by the ICS combination therapy of BFC and CIC-HFA.

The effect of film quality on reading radiographs of simple pneumonconiosis in a trial of x-ray sets.

Post-hoc analysis of two phase III clinical studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequency in patients with severe chronic obstructive pulmonary disease (COPD) who were taking inhaled corticosteroids (ICS) concomitantly, whereas patients not taking ICS derived no such benefit. In contrast, in two different trials also performed in patients with severe COPD, roflumilast reduced exacerbation rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic activity to be realized. Given that roflumilast is recommended as an “add-on” medication to patients with severe disease who will inevitably be taking a long-acting <i>β</i>₂-adrenoceptor agonist (LABA)/ICS combination therapy, we tested the hypothesis that roflumilast <i>augments</i> the ability of glucocorticoids to induce genes with anti-inflammatory activity. Using a glucocorticoid response element (GRE) luciferase reporter transfected into human airway epithelial cells [both bronchial epithelium + adenovirus 12 - SV40 hybrid (BEAS-2B) cells and primary cultures], roflumilast enhanced fluticasone propionate–induced GRE-dependent transcription. Roflumilast also produced a sinistral displacement of the concentration-response curves that described the augmentation of GRE-dependent transcription by the LABA formoterol. In BEAS-2B cells and primary airway epithelia, roflumilast interacted with formoterol in a positive cooperative manner to enhance the expression of several glucocorticoid-inducible genes that have anti-inflammatory potential. We suggest that the ability of roflumilast and formoterol to interact in this way supports the concept that these drugs together may impart clinical benefit beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy. Roflumilast may, therefore, be especially effective in patients with severe COPD.